Fragile X Syndrome

Date First Published: April 2, 2007
Date Last Updated: November 22, 2010

One of the disorders or syndromes known to sometimes co-occur with autism is Fragile X Syndrome.

Fragile X syndrome is a genetic disorder caused by the mutation of a single gene on the X chromosome. The gene, which is supposed to make a protein needed for normal brain development, is turned partially or totally off. ¹  Both boys and girls are affected, but because boys – who have one “X” and one “Y” chromosome -- have no back-up for a problem on the “X” chromosome, they are more severely impacted than girls, who have two “X” chromosomes.

Fragile X is the most common cause of inherited mental retardation, that is, of mental retardation caused by a genetic problem carried down through generations. Individuals with fragile X often suffer a variety of developmental delays, and have a distinct physical appearance including a large head, long face, and prominent ears. ²  About 25-33% of them will also have autism. ^3,4   Those with both fragile X and autism face even more challenges than those with fragile X alone, and early intervention is especially crucial in these cases. ⁵

As for how many individuals with autism also have fragile X, that is still being debated. The figure has been set at anywhere from 1% to 6%. ^6,7   Due to the fact that fragile X was recognized only relatively recently, and is not routinely screened for, it is likely that we are underestimating the prevalence of fragile X among those with ASDs. ⁸ 

Understanding that fragile X and autism often occur together is important both clinically and scientifically. In clinical terms, the connection means that those with autism can be screened for fragile X, while those with fragile X can be carefully watched for signs of autism. Finding out fragile X is playing a role is important to families because the condition is genetic, and can impact other members of the family. For example, the sibling of a child with fragile X, who has been having more mild difficulties, may also be affected by fragile X, though to a different degree. Other relatives, who may be carriers of the condition even if they do not have it themselves, will be able to benefit from genetic counseling when it comes time to make decisions about having children of their own.

In terms of science, it is hoped that the overlap between fragile X and autism may point the way to answers. A diagnosis of autism is currently made based entirely on behavior. There is no known cause, and no known biological marker of the condition. (In other words, you can’t draw a blood sample, look at an MRI, or do a genetic test to tell if a person has autism.) In contrast, a diagnosis of fragile X is made entirely based upon genetics, and the multiple influences of this one gene gone wrong on structure and processing in the brain are at least partially understood. It is hoped that, by using fragile X as a starting point, progress may be made in solving the mysteries surrounding autism.⁹

Related Articles

Fragile X Syndrome: A Genetic Model for Autism with Targeted Treatments
Randi Hagerman, Medical Director of the U.C. Davis M.I.N.D. Institute, explains the important links between fragile X and autism, and how our new understanding of these may lead to effective new autism treatments.

References

1. U.S. Centers for Disease Control and Prevention. (2006). Causes of Fragile X Syndrome. Retrieved on November 22, 2010.
2. U.S. Centers for Disease Control and Prevention. (2006). Fragile X Syndrome. Retrieved on November 22, 2010.
3. Hatton, D.D., Sideris, J., Skinner, M., Mankowski, J., Bailey, D.B., Roberts, J., & Mirrett, P. (2006). Autistic behavior in children with Fragile X syndrome: Prevalence, stability, and the impact of FMRP. American Journal of Medical Genetics Part A, 140A, 1804-1813.  Abstract
4. Zafeiriou, D.I., Ververi, A., & Vargiami E. (2006). Childhood autism and associated comorbidities. Brain & Development, in press, doi:10.1016/j.braindev.2006.09.03 – available on-line 11/7/06.  Abstract
5. Bailey, D.B., Hatton, D.D., Skinner, M., & Mesibov, G. (2001). Autistic behavior, FMR1 protein, and developmental trajectories in young males with Fragile X syndrome. Journal of Autism and Developmental Disorders, 31(2), 165-174.  Abstract
6. Volkmar, F.R., Wiesner, L.A., & Westphal, A. (2006). Healthcare issues for children on the autism spectrum. Current Opinion in Psychiatry, 19, 361-366.  Abstract
7. Hagerman, R.J. (2006). Lessons from Fragile X regarding neurobiology, autism, and neurodegeneration. Developmental and Behavioral Pediatrics, 27(1), 63-74.  Abstract
8. Fombonne, E. (2005). Epidemiological studies of pervasive developmental disorders. In F. Volkmar et al. (Eds.), Handbook of Autism and Pervasive Developmental Disorders (pp.42-69). Hoboken, NJ: John Wiley & Sons. (pg. 51)
9. Belmonte, M.K., & Bourgeron, T. (2006). Fragile X syndrome and autism at the intersection of genetic and neural networks. Nature Neuroscience, 9(10), 1221-1225.  Abstract